Abstract
Forkhead box protein A2 (FOXA2) is a core transcription factor that controls cell differentiation and may have an important role in bone metabolism. However, the role of FOXA2 during osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains largely unknown. In this study, decreased expression of FOXA2 was observed during osteogenic differentiation of rat BMSCs (rBMSCs). FOXA2 knockdown significantly increased osteoblast-specific gene expression, the number of mineral deposits and alkaline phosphatase activity, whereas FOXA2 overexpression inhibited osteogenesis-specific activities. Moreover, extracellular signal-regulated protein kinase (ERK) signalling was upregulated following knockdown of FOXA2. The enhanced osteogenesis due to FOXA2 knockdown was partially rescued by an ERK inhibitor. Using a rat tibial defect model, a rBMSC sheet containing knocked down FOXA2 significantly improved bone healing. Collectively, these findings indicated that FOXA2 had an essential role in osteogenic differentiation of BMSCs, partly by activation of the ERK signalling pathway.
Highlights
Fracture delayed union or non-union is one of the most common complications following fixation, which continues to be a main challenge for orthopaedic surgeons
Level of Forkhead box protein A2 (FOXA2) was decreased in osteogenic-differentiated rat BMSCs (rBMSCs) compared with undifferentiated bone marrowderived mesenchymal stem cells (BMSCs)
To determine the expression level of FOXA2 associated with osteogenic differentiation of mesenchymal stem cells (MSCs), we compared endogenous FOXA2 expression of undifferentiated and osteogenic differentiated rat BMSCs
Summary
Fracture delayed union or non-union is one of the most common complications following fixation, which continues to be a main challenge for orthopaedic surgeons. It has been reported that the overall percentage of delayed union or non-union can be as high as 4.4% of all open fractures[1]. As a major contributor to bone formation, mesenchymal stem cells (MSCs) have been reported to have a key role during fracture healing and have emerged as the most promising candidate for tissue repair[6,7,8]. MSCs are regulated by transcription factors and possess self-renewal capabilities, together with the potential to differentiate into a variety of bone formation-related cell types such as osteoblasts and chondrocytes[9,10,11]. A better understanding of the osteogenic differentiation of MSCs, especially the involvement
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